Alkylene-bis-carbamylamino-and guanidylcyclohexanes



Patented May 1, 1951 V 2,551,378

UNITED STATES PATENT OFFICE ALKYLENE-BIS-CARBAMYLAMINO- AND GUANIDYLCYCLOHEXANES James Emory Kirby, Wilmington, Del., assignor to E. I. du Pont de Nemours & Company, Wilmington, Del., a corporation of Delaware No Drawing. Application November 17, 1948, Serial No. 60,640

f Claims. (01. 260-552) 1 2 This invention relates to nitrogen-substituted wherein n is an integer from one to five, each R dialicyclic compounds and more particularly to is hydrogen or a, methyl radical, not more than new and useful 'amido derivatives of dialicyclic one such methyl radical being present on each of diamines. the rings, each X is oxygen, or sulfur, i. e., a chal- This invention has as an object the preparation 5 cogen of integral atomic number 8n wherein n of new derivatives of dialicyclic diamines. A furis an integer of up to two, and each Y is hydrother object is the preparation of new intermedigen or methylol (--Cl-I2OH). These preferred ates for resins. Another object is the preparacompounds are then the bis-guanidines (iminotion of new pest control agents, and new intercarbamides) the bis-thioureas (thiocarbamides) mediates for pharmaceuticals. Other objects will 10 and the bis-ureas (carbamides) derived from the appear hereinafter. symmetrical-dialicyclic diamines represented by These objects are accomplished by the inventhe general formula, tion of new compounds of the formula x E a wherein n is an integer of from one to five and HNB"(CH1)"-1 BNH NHY B is, a cycloalkylene radical, i. e., a divalent satuwherein n is an integer from one to five, each X rated hydrocarbonfradical having a cyclohexane is oxygen, sulfur, or imino (='NH), each Y is hynucleus, said radical containing at least six and drogen or methylol (-CHzOH), and B is a sixpreferably not more than seven carbons, the two membered divalent alicyclic hydrocarbon radical valen-ces of the radical stemming from ring carhaving a, cyclohexane nucleus and any other hybons of the cyclohexane nucleus, preferably in drocarbon substituent being monovalent hydrothe 1,4-positions to each other, and any hydrocarbon radicals bonded to ring carbon of said carbon substituent on said nucleus being bonded cyclohexane nucleus, Thus the compounds are to a ring carbon which is other than a, radical bis-guanidine (iminocarbamides), bisethioureas valence bearing carbon andv preferably in an (thiocarbamides) and bis-ureas (carbamides) ortho or meta position to thatbearing' the amino derived from dialicyclic diamines represented by group. the formula H2NB--(CH2) n-1BNH2 in The following examples inwhich parts are by which the symbols, n and B, have the same weight are illustrative of the invention. 1

EXAMPLE I' H 7 Preparation of 1,1 (methylenedi 1,4 cyclohemylene) diurea V om-oH, CH -CH, n Her-c cn-on -ofi err-NH; zNmc ONH:

om-c cm-o I o rim-0H, 7 era-on, o

mN-ti-nn-o cn-omr-o oH-NH-c-NH, 2NH;

GHQ-'0 l CHz-C 2 Formula A meaning as indicated above for the new com- 5 A mixture of 9 parts of urea and 10.5 parts of pounds of the invention. di(4-aminocyclohexyl)methane (prepared as de- A preferred embodiment of the invention c0mscribed in the copending application of. Kirk, prises the new symmetrical compounds repre- Schreiber and Whitman, Serial No. 615,912, filed sented by the formula 7 September 12, 1945, now abandoned by the hydro X I ore-0H, 011 03 X YHNlL-HN-Cfi CH-(CHn),.-1--C CHNHg-NHY 1 t. it

genation at 100 C. and a hydrogen pressure of 135 atmospheres of di(p-aminophenyl) methane in dioxane over ruthenium dioxide) was heated gradually to 140 C. where it was maintained for extract was successively washed with dilute sodium hydroxide, dilute hydrochloric acid and finally with water. After drying the ether extract over calcium chloride and removal of the ether by distillation, 374 parts of crude, yellow,

1.5 hours. At this point, ammonia evolution, 5 which had started at about 110 0., ceased. oily product was obtained. Crystallization of this The solid white residue (11 parts) remaining oily product was induced by stirring with 200 after extraction of the hard reaction product parts of methanol at room temperature and the with 1450 parts of boiling water was, as shown resulting solid, which was separated by filtration, by analysis, 1,1'-(methylenedi-1,4-cyclohexylwas subsequently recrystallized from a mixture ene)diurea (see Formula A) melting above 230" of 240 parts of n-butanol and 200 parts of C. AnaZysis.Calculated for C15H2aN4O22 N, methanol. This yielded, after filtration and dry- 18.9%. Found: N, 18.69%; 19.02%. ing, 1845 parts of crystalline methylenedi-L4- cyclohexylene diisothiocyanate. AnaZysz's.Cal- EXAM} 15 culated for C15H22N2S2! c, 61.2%; H, 7.5%; N, Preparation of 1,1'-(methyZenedi-I,4-cycloheryl- 9.5%; s, 21.8%. Found: C, 61.0%; H, 7.7%; N.

ene)bis(2-thiourea) 9.3%; S, 21.7%. r l b. 1,1-(METHYLENEDI-1,4-CYCLOHEXYLENE)BIS H,N-oHN-o oH-om-ofi CH-NHC-NH; (ZTHIOUREA) CH C CH g Product of above Formula D+2NH3(C4H9OH)- r 2 r bis-thiourea of Formula B Formula. B

One hundred (100) parts of the diisothiocyagfg '%6%%% Q%% nate' prepared as described above was refluxed CHI-CH! CHg-CH; H,No on-om-ofi on mzr, ms. zmon CHI-O CHz- 1 CHr-CH; CHI-CH, NaS-C-HN-Ofi CHCH;O\ CHNHC|J-SNa zmo CHI-C GET-C Formula C zl 01o 0001B! cHi-cfla GHQ-CH2 soN-c on-om-cfi CHNOS 2NaCl 200s 20.115011 CHg-C 1 GHQ-C z I Formula D A solution of 284 parts of di(4-aminocyclohexyD-methane, and 103 parts of dioxane was added dropwise to a stirred mixture of 208 parts of carbon disulfide, 108 parts of sodium hydroxme and 800 parts of water. During this addition, the temperature of the reaction mixture was allowed to rise from 20 C. to C. after with 243 parts of n-butanol until a clear solution was obtained. Ammonia gas was then bubbled into this refluxing (114 C.) solution for eight hours. The solution was cooled in ice and the resulting white crystalline l,1'-(methylenedi-1,4- cyclohexylene)bis(2-thiourea) [see above Formula B] which was filtered, washed with acetone which the mixture was heated cautiously on the and dried amounted to 74 parts. AnaZysis.- steam bath for 0.5 hour, being careful to avoid Calculated for C15H2BN4Sz: N, 17.0%. Found: foaming. The resulting suspension of disodium N, 16.99%; 16.84%.

EXAMPLE III Preparation of 1,1-(methylenedi-I,-cyclohewylene) diguanidine CHr-CH, CHz-CH: NH HgN-H H-C'Hr- H JH-NH +2[CH S J-NH ]1.HgSO4 Hr- H'] Hr- Hg cal-on, om-on, [H N-C-HN-CH tit-enr- H H-NH- o-NH,:| mso. zcmsn I H Hg-Hz lHr-JIH: H

Formula E salt of N.N'-(methylenedi-1,4-cyclohexylene) bis- (thiocarbamic acid) [see Formula C] was then Chemically equivalent amounts of di(4-aminocyclohexyD-methane (21 parts) and S-methyl-- cooled to about 40 C. and 32-1 parts of ethyl isothiourea sulfate (27.8 parts) were heated in chlorocarbonate added dropwise with stirring. The mixture was then heated on a steam bath for 0.5 hour. After cooling to room temperature, the separated oily solid was extractedfrom the a methanol/water (10 parts/65 parts) solution on-the steam bath for one hour when evolution of methyl mercaptan, very rapid at the beginning of the reaction, had practically ceased. Most of reaction mixture with diethyl ether- The ether 75 the solvents were then removed by distillation being collected in water.

tion was next treated with an excess of EXAMPLE IV was added 33 parts of '1,l'-(methy1enedi-1,4- cyclohexylene)-diurea (Formula A) and 125 parts of n-butanol. This was heated at 95-100 C. until a clear solution was obtained. To this solution of 1,1-(methylenedi-1,4-cyclohexylene)bis [(3-n-butoxymethylurea)] (see above Formula G) was added parts of toluene and 0.63 part of phthalic anhydride and the mixture Preparation of 1,1 (methylenedi-I,4-cyclohemylene} bis (3-hydroazymethylurea.)

H Product of above Formula A ZHC-E CHzCH:

CH-CHr-C CH3-C2 Formula F A mixture of 53 parts of 1,1-(methylenedi- 1,4-cyclohexy1ene)diurea and parts of 37% formaldehyde adjusted to a pH 8.89.0 was heated for two hours wth stirring at -90 C. After cooling, the resulting gummy solid methylol clerivative [see Formula F] was removed, washed thoroughly with water and dried. The thoroughly dried product was then ball-milled to liberate unreacted formaldehyde. Analysis of this dimethylol derivative was carried out by determining the formaldehyde content in accordance with the following procedure. A weighed sample was digested under reflux with aqueous 40-50% phosphoric acid. After said digestion, the formaldehyde liberated was distilled as aqueous formaldehyde, the condensate The condensate soluaqueous sodium sulfite solution and the sodium hydroxide which was formed according to the equation (sodium formaldehyde sulfoxylate), was titrated with dilute hydrochloric acid using phthalein or other suitable indicator. By this method, the formaldehyde content of two samples of the above dimethylol derivative was determined as 16.50% and 17.01% respectively, which compares with 16.85% for the calculated value. 7

The above product mixed with glycolic acid (0.5% based on the weight of the methylol product) catalyst readily molded into bars at 150 C. under pressures of 1000-2000 lbs/sq. in. and" a molding cycle of 5 minutes. These molded bars possessed Izod impact strengths of 0.24 to 0.30 ft. 1b./in. and a Rockwell hardness value of 120.

EXAMPLE V thymol- I ,H2NCONH groups respectively. methylol derivatives the terminal amido hydro- Gila-C 2 CHz-C a was refluxed, water being removed from the reaction as formed. When water ceased to come off, all volatile material up to a pot temperature of C. was distilled.

The resultant resin solution was used to flow films on phosphate-treated rust-resistant steel panels and the films were then baked at C. for one hour. These films possessed excellent water and alkali (0.1 N-sodium hydroxide) resistance after 15 hour contacts at room temperature. The hardness of these films corresponded to a pencil hardness of 3H.

The present invention is generic to the new compounds of the formula is oxygen, sulfur, or imino (=NH), each Y is hydrogen or methylol (-CH2O=H), and B is a sixmembered divalent alicyclic hydrocarbon radical having a cyclohexane nucleus and any other hydrocarbon substituent being monovalent hydrocarbon radicals bonded tov ring carbon of said cyclohexane nucleus. Thus the compounds are bis-guanidines (iminocarbamides), bis-thioureas (thiocarbamides) and bis-ureas (carbamides) derived from dialicyclic diamines represented by the formula in which the symbols, n and B, have the same meaning as indicated above for the new compounds of the invention. In these derivatives the H2N groups of the diamines are replaced by HzN-C (=NH) NI-I--, and

In the 1,1 (methyZenedi-I,4-cyclohexylene) bis [(3-n-butoxymethylurea) l Product of above Formula A 235 -11 N-C H OH (Excess) the following procedure. To a solution of 22.5 parts of 37% formaldehyde and0.32 part of .monobasic sodium phosphate (NaH2PO4.H2O) adgen is replaced by HOCH2 groups and although 'the invention has been illustrated in particularity, other dialicyclic diamines which can be suitably employed in the examples in place of di (4- justed to a;pH of 8 with 5% sodium hydroxide 75 aminocyclohexybmethane for the preparation of the new compounds of the invention include d'i(4-aminocyclohexyl), [(Balas and Sevcenko, Collection Czechoslov. Chem. Communications 3, 171-6 (1931) bis(4-amino-3-methylcyclohexyl),bis(4 amino 3 methylcyclohexyD- methane, 1,2 bis'(4 aminocyclohexyl) ethane and 1,3 bis(4. aminocyclohexyDpropane as prepared by the hydrogenation, at 75-250 C. and a hydrogen pressure of at least 100 lbs/sq. in., of the corresponding amino-, nitro-, or nitroso-phenyl compound over ruthenium dioxide catalyst, as disclosed in the application of Kirk et al., Serial No. 615,912, filed September 12, 1945; bis(4 amino-2-methylcyclohexyl)methane (prepared by the hydrogenation at 75-250 C. and a hydrogen pressure of 1500-2700 lbs/sq. in. of 2,2-dimethyl-4,4-diaminodiphenylmethane as disclosed in Bolton and Kirk, Serial No. 615,918, filed September 12, 1945, now U. S. Patent 2,5 12,606) 1,4-bis l-aminocyclohexyl) butane [Ferber, 138126213 192 (1929)]. Because of their cheapness and satisfactory reactivity to yield the new carbamido compounds of the invention, the dialicyclic diamines, such as those just men tioned, which contain two saturated six-membered cycloaliphatic rings having up to seven carbons are preferred.

Of the new compounds of the invention, the bis-ureas and bis-thioureas, i. e., those carbamido compounds defined by the structural formula in column 1 wherein Y is hydrogen and X is a chalcogen (oxygen or sulfur) of integral atomic number 8n, n being an integer of up to two, are preferred since they are usually the most easily prepared. The most preferred are the bis-ureas because they are readily derived in highest yield from low cost urea by reaction with the dialicyclic diamines and, moreover, they can be smoothly and economically converted by formaldehyde condensation to the methylol derivatives from which the cheapest and most attractive molded articles have been produced.

While other well-known methods can usually be employed to prepare the new carbamido compounds of this invention, the processes described in the examples are, in general, satisfactory and preferred. Employing the method of the examples for the preparation of the bis-ureas of the invention, the m'olal ratio of the dialicyclic diamines to urea may vary between 1:1 to 1:5 or more. It is preferable, however, to use a molal excess of urea. The reaction may be satisfactorily operated at temperatures of from 80-200 0., depending to a large extent on the dialicyclic diamine being treated. In general, the preferred temperature is between 125-l60 C. The time of reaction can vary widely, for example, from 1 to 24 hours or more, depending on the temperature and the attendant rate of ammonia evocause solution of the diisothiocyanate at the reaction temperature, 100-150 C. Reaction time can vary from 1 to 24 hours or more, but usually 5 to 15 hours is sufiicient time for satisfactory results.

For the preparation of the bis-guanidines, it is preferable to use at least chemically equivalent amounts of the S-alkyl isothiourea, for example, S-methyl, 'S-ethyl, etc., or the corresponding mineral acid salts such as the hydrochlorides or sulfates, and the dialicyclic diamines at temperatures (150 C.) Where alkyl mercaptan is evolved at a satisfactory rate. Although the reaction may be carried out without diluent it is preferable to employ diluents such as water, organic solvents, such as alcohols, e. g., methanol, ethanol, propanol, butanol, etc., or mixtures of organic solvents and water.

Although the methylol derivatives of the invention, for example, the methylol derivatives of the bis-ureas, can be produced by the use of the chemically equivalent amounts of formaldehyde, it is preferable to operate with molal excesses, for example, -500% excesses, of this aldehyde. Aside from the n-butanol shown in the example, other alcohols, for example, ethanol, propanol, butanol, pentanol, etc., may be used for the condensation reaction of the herein described carbamido compounds with formaldehyde. Such formaldehyde condensation, whether in an alcohol or water medium, iscarried out at a pH of from 7 to 11, preferably 8 to 9.5 and at a temperature of B O- C.

With the exception of the methylol derivatives which are for the most part amorphous solids, the new carbamido compounds of this invention are, ordinarily,'high melting crystalline solids insoluble in water and most organic solvents such as ethanol, benzene, acetone, etc. The methylol derivatives, although substantially insoluble in water and hydrocarbon solvents, are appreciably soluble in acetone, alcohols, e. g., ethanol, propanol, butanol, etc.

In addition to the use of the new compounds of this invention as resin-forming materials for application in the manufacture of molded articles and coating compositions, they are also useful as intermediates for pharmaceuticals and as pest control agents, particularly the bis-thioureas for the insect-proofing of woolen fabrics.

The foregoing detailed description has been given for clearness of understanding only and no unnecessary limitations are to be understood therefrom. The invention is not limited to the exact details shown and described for obvious modifications will occur to those skilled in the art.

What is claimed is: 1. A symmetrical compound of the formula lution, a criterion of the completion of the reacwherein n is an integer from one to five, each Y tion. High boiling, inert, organic solvents may be used but these are not ordinarily required.

Likewise in the preparation of the bis-thioureas of the invention, the molal ratio of the dialicyclic diisothiocyanate to ammonia may vary between 1:1 to 1:20 or more. The reaction is, in general, most suitably conducted with molal excesses of ammonia and preferably with polar organic solvents, such as butanol, pentanol, cyclohexanol,

is the same member of the class consisting of hydrogen and methylol, each X is the same member of the class consisting of O, S, and NH, and each R is a member of the class consisting of hydrogen and monovalent saturated hydrocarbon radicals.

2. A compound according to claim 1 wherein X is a chalcogen of integral atomic number of Sn,

dioxane, etc., employed in amounts suflicient to 7 n being a positive integer not greater than 2.

1 3. A symmetrical compound of the formula 0 CHr-CH: GHQ-CHI mN-ox-Nn-c \m-wmn-cfi CH-NHCX--NH| cm-c cm-c I wherein each X is the same chalcogen of atomic 4. A compound of the formula CHI-CHI OBI-CH mN-o o-mr-c cn-cm-c CH--NHC o-Nm CHs-C CHr-C I weight not greater than 33 and m is a. cardinal a A compound f the 10mm number not greater than 4.

CHI-CH1 Gag-CH nm-cs-un-cfi cm-cm-o cH-Nn-cs-NH,

CHI-'0 CHI-C 1 JAMES EMORY KIRBY.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,145,242 Arnold Jan. 31, 1939 2,347,827 Hunt May 2, 1944 

1. A SYMMETRICAL COMPOUND OF THE FORMULA
 5. A COMPOUND OF THE FORMULA 